Chapter title |
Independent-Trajectory Thermodynamic Integration: A Practical Guide to Protein-Drug Binding Free Energy Calculations Using Distributed Computing
|
---|---|
Chapter number | 27 |
Book title |
Computational Drug Discovery and Design
|
Published in |
Methods in molecular biology, January 2004
|
DOI | 10.1007/978-1-61779-465-0_27 |
Pubmed ID | |
Book ISBNs |
978-1-61779-464-3, 978-1-61779-465-0
|
Authors |
Morgan Lawrenz, Riccardo Baron, Yi Wang, J. Andrew McCammon, Lawrenz, Morgan, Baron, Riccardo, Wang, Yi, McCammon, J. Andrew |
Abstract |
The Independent-Trajectory Thermodynamic Integration (IT-TI) approach for free energy calculation with distributed computing is described. IT-TI utilizes diverse conformational sampling obtained from multiple, independent simulations to obtain more reliable free energy estimates compared to single TI predictions. The latter may significantly under- or over-estimate the binding free energy due to finite sampling. We exemplify the advantages of the IT-TI approach using two distinct cases of protein-ligand binding. In both cases, IT-TI yields distributions of absolute binding free energy estimates that are remarkably centered on the target experimental values. Alternative protocols for the practical and general application of IT-TI calculations are investigated. We highlight a protocol that maximizes predictive power and computational efficiency. |
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